The present invention relates to pharmaceutical formulations of a family of bisbenzylisoquinoline alkaloids. The specific family is referred to herein as the “tetrandrine family.”
The tetrandrine family bisbenzylisoquinolines have two nitrogen locations and hence can exist in the free base form or as a mono or di-acid salt. Because of the enhanced solubility of the salt form of pharmaceutical ingredients, the salt forms are used in formulating pharmaceutical compositions. The active ingredient thus solubilizes more quickly and enters the bloodstream faster.
However, the di-acid chlorides of the tetrandrine family members, most importantly the dihydrochloride (DHC), are a difficult molecule to produce using standard pharmaceutical processing. As a result, all known formulators in the world use an in situ procedure as part of the compounding methodology. This leads to variations in content uniformity and tablet-to-tablet potency variances.